Efficacy and safety of 5 mg olanzapine combined with aprepitant, granisetron and dexamethasone to prevent carboplatin-induced nausea and vomiting in patients with gynecologic cancer: A multi-institution phase II study

• Published in: Gynecologic oncology 2020-03, Vol.156 (3), p.629-635
• Main Authors: Iihara, Hirotoshi, Shimokawa, Mototsugu, Hayasaki, Yoh, Fujita, Yukiyoshi, Abe, Masakazu, Takenaka, Motoki, Yamamoto, Senri, Arai, Takahiro, Sakurai, Michiru, Mori, Minako, Nakamura, Kazuto, Kado, Nobuhiro, Murase, Saki, Shimaoka, Ryuichi, Suzuki, Akio, Morishige, Ken-ichirou
• Format: Article
• Language: English
• Subjects: Carboplatin; Gynecological cancer; Nausea; Olanzapine; Vomiting
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2020.01.004

The aim of this study was to investigate the efficacy and safety of prophylactic administration of 5 mg olanzapine (OLZ) combined with neurokinin 1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5-HT3RA), and dexamethasone (DEX) to prevent nausea and vomiting in carboplatin (CBDCA) combination therapy for patients with gynecological cancer. We conducted a single-arm, multi-institution, phase II study. Gynecological cancer patients scheduled to receive AUC ≥4 mg/mL/min CBDCA were enrolled. All patients received 5 mg OLZ (once daily after supper on days 1–4) combined with NK1RA, 5-HT3RA, and DEX. The primary end point was complete response (CR; no emesis and rescue therapy) during overall phase (120 h after the start of carboplatin administration). Between May 2018 and June 2019, 60 patients were enrolled from 3 institutions in Japan. A total of 57 patients who met the criteria were included in the efficacy and safety analysis. The CR rate for the overall phase was 78.9%. Acute (0–24 h) and delayed phases (24–120 h) were 96.5% and 80.7%, respectively. Somnolence was observed in 73.7% patients. However, somnolence of grade 2 or higher was observed in only 3.5% of cases. There were no grade 3 or 4 toxicities associated with OLZ. Preventive use of OLZ combined with standard triplet therapy had promising activity with manageable safety, suggesting that this combination could be an effective standard treatment option for patients with AUC ≥4 mg/mL/min CBDCA combination therapy. •This is the first trial to evaluate 5 mg olanzapine for carboplatin-based chemotherapy in gynecologic cancer patients.•Preventive use of 5 mg olanzapine combined with standard triplet antiemetic therapy has promising activity.•Olanzapine was tolerated with low grade somnolence and decreased concentration.•>90% of patients reported they were very satisfied or satisfied with olanzapine combined regimen.